QLT Inc. announced results of its phase II clinical study on the efficacy and safety of the Latanoprost Punctal Plug Delivery System (LPPDS) in subjects with Ocular Hypertension (OH) and Open-Angle Glaucoma (OAG).
The phase II trial featured simultaneous placement of punctal plugs in both the upper and lower puncta for delivery of a daily drug load with a goal of enabling comparable clinical outcomes to that of daily administered Xalatan eye drops. The company’s overall drug development objective was a mean reduction in IOP of 5 mmHg or greater. The primary endpoint in this phase II study was the mean change in IOP from baseline (measured as mmHg) at 2 weeks. Secondary endpoints were the mean change in IOP from baseline at 4 weeks and mean percentage change in IOP from baseline at 2 weeks and 4 weeks.
A total of 95 ITT (Intent to Treat) subjects were included in the L-PPDS treatments in this study. The mean IOP at baseline was 25.8 mmHg for this group. After 2 weeks of L-PPDS treatment, IOP showed a statistically significant mean change from baseline of -6.2 mmHg (95% C.I. -6.8, -5.6). At the end of 2 weeks, 73% of subjects showed an IOP reduction vs. baseline of 5 mmHg or greater and 51% of subjects showed a reduction of 6 mmHg or greater. The mean percentage change in IOP from baseline at 2 weeks was -24.3%, which was statistically significant (95% C.I. -26.7, -21.9).
After 4 weeks of L-PPDS treatment, IOP showed a statistically significant mean change from baseline of -5.7 mmHg (95% C.I. -6.5, -4.9). At the end of 4 weeks, 60% of subjects showed an IOP reduction vs. baseline of 5 mmHg or greater and 47% of subjects showed a reduction of 6 mmHg or greater. The mean percentage change in IOP from baseline at 4 weeks was also statistically significant at 22.3% (95% C.I. -25.4, -19.2). Results reported in earlier phase II L-PPDS studies using different L-PPDS plug designs and doses did not achieve these levels of IOP reduction over a 4 week treatment period.
“Most if not all glaucoma specialists would agree that eye pressure lowering should be taken out of the patients’ hands and left in the hands of the physician,” said Alan L Robin, MD, Associate Professor Ophthalmology and International Health at Johns Hopkins University and Clinical Professor of Ophthalmology, University of Maryland. “The results of the QLT study find the L-PPDS may offer a breakthrough in the way glaucoma medication can be delivered. The results suggest that the L-PPDS may have the ability to deliver long-lasting clinically significant eye pressure lowering that is relatively welltolerated by patients so that they do not have to worry about eye drop instillation. Adherence no longer becomes a factor in preventing the development of needless blindness. Additionally, the procedure appears to be relatively safe, minimally-invasive and simple to perform. With further development success, this delivery system could potentially revolutionize our therapy of glaucoma.”
“We are very excited to see clinically meaningful data showing that a higher dose of latanoprost administered through a double plug approach can successfully decrease IOP by more than 5 mmHg,” said Bob Butchofsky, president and CEO of QLT Inc. “As a result, we plan to move forward with another phase II trial in glaucoma and broaden this delivery platform by accelerating plans for a second molecule in 2012.”
The trial utilized the Company’s newest version of its later stage proprietary punctal plug in the lower punctum and an early stage prototype upper punctal plug based on a modified commercially available plug, providing a combined latanoprost amount of 141 µg. The proprietary lower punctal plugs were retained in 95% of subjects at 4 weeks. The modified commercially available upper punctal plugs were retained in 45% of subjects at 4 weeks. Using a 4 week benchmark, the subject retention rate for the proprietary lower punctal plug designs utilized in previous studies was 49% - 90%.
The L-PPDS was well tolerated over the testing period with adverse events (AEs) similar to those reported for commercial punctal plugs. The majority of AEs were ocular in nature, with tearing reported as the most frequent. No associated AEs were serious. As assessed by subjective scoring by study subjects, tearing was rated predominantly for L-PPDS treated eyes at week 4 as occasional - 22%, mild - 31%, or moderate - 32%. Few subjects experienced any discomfort related to the punctal plugs with most patients having either no awareness or mild awareness of the punctal plugs by week 4 (87% of eyes for LPPDS subjects). A total of 42 subjects were not included in the ITT analysis at week 4, with 34 of these due to losses of the early stage prototype upper plug. During the study, 5 subjects discontinued due to AEs, and 3 subjects discontinued for other reasons. All subjects were included in the safety analysis.
This completed phase II multicenter study was conducted to evaluate the safety and efficacy of the LPPDS utilizing simultaneous placement of punctal plugs in the upper and lower puncta containing a combined total of 141 µg of latanoprost, a prostaglandin analogue, in subjects with ocular hypertension (OH) or open-angle glaucoma (OAG) over a 4 week period. The original study design randomized subjects into one of two treatment groups: placebo/L-PPDS (4 weeks placebo + 4 weeks L-PPDS), and sham/Xalatan (4 weeks sham + 4 weeks Xalatan drops). In April 2011, the trial design was amended to remove the sham/Xalatan arm and to remove an initial 4 week placebo plug period from the study. These changes simplified the trial design and provided earlier access to active treatment in the study, which reduced the rate of patient discontinuation in the trial. The Principal Investigator for the study was Dr Robert Williams, formerly of the Taustine Eye Centre in Louisville, KY.
Research and Development (R&D) expense in the first half of 2011 was $ 21.1 million, and the Company previously provided guidance for R&D expense of approximately $ 10 million to $ 12 million for the third quarter of 2011. With the results of the phase II L-PPDS study in hand, the Company is now providing R&D guidance for full year 2011 of $ 44 million to $ 46 million. Major R&D initiatives for the remainder of the year relating to the QLT091001 Phase 1b trial in patients with Leber Congenital Amaurosis (LCA) and Retinitis Pigmentosa (RP) include: ongoing follow-up of LCA patients, initial re-treatment of LCA patients treated in the trial, completion of enrollment in the RP cohort, and ongoing formulation and development work. For the punctal plug drug delivery program, near term development goals include further evaluation of the single versus double plug approaches and enabling a longer duration of sustained release. Major R&D plans for this program include commencing another phase II trial in glaucoma, device work in particular for upper puncta placement, and ongoing formulation and development work in particular for new product candidates.
QLT is an ocular-focused company dedicated to the development and commercialization of innovative ocular products that address the unmet medical needs of patients and clinicians worldwide.